We propose to "rescue" lymphoma-bearing mice from lethal doses of anti-cancer drug, Methotrexate (MTX) with N5-methyltetrahydrofolate (NMTF) when the animals are maintained on a methionine-free diet, containing DL-homocystine as the only sulfur amino acid. Preliminary studies support the concept that the regimen we propose may provide selective "rescue" of normal cells in the presence of the L-1210 and L-5178Y neoplastic cells, which are known to be methionine-dependent. We plan to monitor the effects of both the diet and the drug treatments on the levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the livers of treated animals. The ratio of SAM/SAH is important in the control of biological methylation reactions. By exploring the effects of the "rescue" protocol on survival and on SAM/SAH ratios in the liver of tumor-bearing animals, we shall be expanding current understanding of the molecular nature of sensitivity to MTX and its effects on the metabolism of sulfur amino acids, which play a fundamental role in all biological methylations.